Reliable performance of neural recording electrodes continues to be a very significant hurdle in successful clinical application of neuroprosthetics. Although progressive astrocytic encapsulation and neuronal loss/degeneration have been implicated as principal mechanisms of neuroelectrode failure, recent work has found evidence that persistent inflammation and neurovascular (BBB) compromise may have a more significant role than previously understood. Supplementing animal models, we propose to use a novel microfabricated device that recapitulates essential functions of the neurovascular unit, enabling the study of tissue response in a controlled fashion and the role of neuroinflammation after probe implantation. Our concept features a neural parenchyma (3-D mixture of neurons, astrocytes, and microglia) in communication with microvascular endothelial cells exposed to flow. In preliminary work we have successfully fabricated test devices, characterized barrier properties, and neuroglial-vascular communication within the device. The first aim will quantitatively assess the tissue reaction to two different probes and validate the model response using known in vivo data. In the second aim, we will provide proof-of-principle and preliminary insights on the dynamic interplay of neuroinflammation and glial encapsulation, using circulating monocytes and anti- inflammatories. Our long term objective is to develop an automated instrument for mechanistic understanding and screening of novel probe designs, with general applicability towards other CNS disorders.